Mantle Cell Lymphoma Relapsing at the Lymphedematous Arm
Giuseppina Massini1, Stefan Hohaus1, Francesco D’Alo',1, Valentina Bozzoli1, Barbara Vannata1, Luigi Maria Larocca2 and Luciana Teofili1
1
Departments of Hematology, Catholic University, Rome.
2 Departments of Pathology, Catholic University, Rome.
2 Departments of Pathology, Catholic University, Rome.
Correspondence
to:
Luciana Teofili, MD, Department of Hematology, Catholic University of
Rome, Largo Gemelli 8, 00168 Rome. Tel. 39-6-30154180, Fax
39-6-3055153. E-mail: lteofili@rm.unicatt.it.
Published: February 16, 2013
Received: December 18, 2012
Accepted: February 6, 2013
Meditter J Hematol Infect Dis 2013, 5(1): e2013016, DOI 10.4084/MJHID.2013.016
This article is available on PDF format at:
This is an Open
Access article
distributed under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0),
which permits
unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited
Abstract
Lymphedema
(LE) is a chronic medical condition characterized by lymphatic fluid
retention, resulting in tissue swelling. Cancer treatments involving
lymph nodes can damage lymph drainage routes, causing accumulation of
lymph fluid in the interstitial tissue of related limbs and body areas
and secondary LE. Basically, the LE has a negative impact on physical
and mental quality of life. Moreover, 0.07-0.04% of long term survivors
(most patients undergoing mastectomy) can develop the Stewart-Treves
syndrome, a rare and aggressive multifocal lymphangiosarcoma arising
within the LE region. Here we describe the case of a 45-year-old woman
with a massive LE of the left arm, as a consequence of previous breast
cancer, who was diagnosed after 4 years of stage IV mantle cell
lymphoma (MCL). The patient, after obtaining complete remission with
chemotherapy and autologous hematopoietic stem cell transplant, had a
relapse of MCL in the lymphedema site.
Lymphedema
(LE) is a chronic medical condition characterized by lymphatic fluid
retention, resulting in tissue swelling. Cancer treatments involving
lymph nodes can damage lymph drainage routes, causing accumulation of
lymph fluid in the interstitial tissue of related limbs and body areas
and secondary LE. Recently, Paskett et al. reviewed risk factors,
diagnosis and treatment of cancer related LE.[1]
The
authors underlined that LE cannot be cured but it can only be managed
in order to decrease limb size, improve limb function and prevent
possible complications.[1]
Basically, the LE has a negative impact on physical and mental quality
of life.[1]
Moreover, 0.07-0.04% of long term survivors (most patients undergone
mastectomy) can develop the Stewart-Treves syndrome, a rare and
aggressive multifocal lymphangiosarcoma arising within the LE region.[2]
The pathogenesis of this disease is not fully understood, even
though a causative connection with chronic LE is evident.[2]
The differential diagnosis of Stewart Treves syndrome includes breast
carcinoma metastatic to the skin, sarcoma of Kaposi, melanoma and
cutaneous tumours other than lymphangiosarcomas.[2]
Overall, the prognosis Stewart-Treves syndrome is very poor, with a
median survival of 2.5 years after diagnosis.[3]
The scarce delivery of antiproliferative drugs to the lymphedematous
tissues most likely contributes to the resistance to chemotherapy
observed these patients.[3] The
overall prevalence of LE has been estimated as 0.13–2% in
industrialized countries.[4]
The number of patients with LE is expected to increase significantly
over the next decades because of improved survival rates following
cancer treatment. Indeed, it is conceivable that patients suffering
from chronic LE would develop new cancer.
Case report
A 45-year-old woman with stage IV mantle cell lymphoma (MCL) was recently admitted to our hematology department. She had a massive LE of the left arm, as a consequence of previous breast cancer, treated four years before with radical mastectomy, radiation and chemotherapy. The patient received four courses of R-CHOP (Rituximab 350 mg/m2 day 1, cyclophosphamide 750 mg/m2 iv day 1, doxorubicin 50 mg/m2 iv day 1, vincristine 1.4 mg/m2 ev days 1 and prednisone 1mg/m2 days 1-5), followed by three courses of R-MiCMA5 (Rituximab 350 mg/m2 day 1, Mitoxantrone 10 mg/m2 iv day 1, Carboplatin 100 mg/m2 iv days 1-4; Aracytin 2000 mg/m2 iv day 5 and Methylprednisolone 500 mg/m2 iv days 1-5) with haematopoietic stem cells (HSC) harvesting. The patient achieved complete remission and underwent autologous HSC transplantation as consolidation therapy. The post-transplant follow-up was uneventful for one year, when patient was again admitted to our department with a massive dissemination of purplish cutaneous nodules, in part ulcerated and infected, over the entire surface of the lymphedematous arm (Figure 1). She referred the appearance of small nodules on her left wrist two months before, which progressively sprouted over the entire arm without any systemic symptoms. The lesions were strictly confined to the area of chronic LE, reminding the clinical picture of the Stewart-Treves syndrome (Figure 1). A total body CT scan was performed, but no findings consisting with nodal or parenchymal lymphoma localizations were found. Moreover, bone marrow biopsy showed no lymphoma cell infiltration. The skin biopsy showed multinodular infiltration of lymphomatous cells (Figure 1) that at immunohistochemistry resulted CD20/CD5/CyclinD1positive, with a proliferative index of 90%. Patient received few courses of bortezomib and liposomal doxorubicin, without benefits; she died after few months with widespread pulmonary infiltration by MCL.
Figure 1. The photo shows the massive dissemination of cutaneous lesions over the entire arm surface, appearing as confluent nodules, partially ulcerated and infected. All lesions were confined to the region of LE. The biopsy revealed the multinodular infiltration of lymphoid cells (hematoxylin and eosin staining, 40x magnification).
Discussion
There are few cases reported in the literature on malignant lymphomas arising in a lymphoedematous arm, which can sometimes simulate the Stewart-Treves syndrome.[6] The awareness of this possibility might help in the differential diagnosis of a suspicious cutaneous lesion within the LE. The MCL, in particular, is characterized by the striking tendency to disseminate throughout the body, infiltrating the lymphoid tissues, bone marrow and extranodal sites.[7] Indeed, the aggressive clinical course observed in our patient is not surprising. However, we would like to stress that, at relapse, our patient had no localizations further than those in the lymphedematous arm. This finding suggests that LE could have favoured the persistence of an occult localization of lymphoma, despite routine investigations evidenced an apparent complete remission of disease. Actually, the impaired lymphatic drainage could have rendered the involved area like a “pharmacologic sanctuary”, allowing lymphoma cells to skip the antiproliferative effect of chemotherapy. In addition, the eventual local immuno-deficiency, according to the hypothesis of the “immunocompromised district”, might have promoted the chemotherapy resistance of malignant cells.[8,9]
In conclusion, our experience emphasizes that, in assessing the response to chemotherapy of lymphoma patient with chronic LE, in addition to routine examinations, it should be performed a careful investigation of the involved extremity tailored to exclude residual tumour localizations.
Case report
A 45-year-old woman with stage IV mantle cell lymphoma (MCL) was recently admitted to our hematology department. She had a massive LE of the left arm, as a consequence of previous breast cancer, treated four years before with radical mastectomy, radiation and chemotherapy. The patient received four courses of R-CHOP (Rituximab 350 mg/m2 day 1, cyclophosphamide 750 mg/m2 iv day 1, doxorubicin 50 mg/m2 iv day 1, vincristine 1.4 mg/m2 ev days 1 and prednisone 1mg/m2 days 1-5), followed by three courses of R-MiCMA5 (Rituximab 350 mg/m2 day 1, Mitoxantrone 10 mg/m2 iv day 1, Carboplatin 100 mg/m2 iv days 1-4; Aracytin 2000 mg/m2 iv day 5 and Methylprednisolone 500 mg/m2 iv days 1-5) with haematopoietic stem cells (HSC) harvesting. The patient achieved complete remission and underwent autologous HSC transplantation as consolidation therapy. The post-transplant follow-up was uneventful for one year, when patient was again admitted to our department with a massive dissemination of purplish cutaneous nodules, in part ulcerated and infected, over the entire surface of the lymphedematous arm (Figure 1). She referred the appearance of small nodules on her left wrist two months before, which progressively sprouted over the entire arm without any systemic symptoms. The lesions were strictly confined to the area of chronic LE, reminding the clinical picture of the Stewart-Treves syndrome (Figure 1). A total body CT scan was performed, but no findings consisting with nodal or parenchymal lymphoma localizations were found. Moreover, bone marrow biopsy showed no lymphoma cell infiltration. The skin biopsy showed multinodular infiltration of lymphomatous cells (Figure 1) that at immunohistochemistry resulted CD20/CD5/CyclinD1positive, with a proliferative index of 90%. Patient received few courses of bortezomib and liposomal doxorubicin, without benefits; she died after few months with widespread pulmonary infiltration by MCL.
Figure 1. The photo shows the massive dissemination of cutaneous lesions over the entire arm surface, appearing as confluent nodules, partially ulcerated and infected. All lesions were confined to the region of LE. The biopsy revealed the multinodular infiltration of lymphoid cells (hematoxylin and eosin staining, 40x magnification).
Discussion
There are few cases reported in the literature on malignant lymphomas arising in a lymphoedematous arm, which can sometimes simulate the Stewart-Treves syndrome.[6] The awareness of this possibility might help in the differential diagnosis of a suspicious cutaneous lesion within the LE. The MCL, in particular, is characterized by the striking tendency to disseminate throughout the body, infiltrating the lymphoid tissues, bone marrow and extranodal sites.[7] Indeed, the aggressive clinical course observed in our patient is not surprising. However, we would like to stress that, at relapse, our patient had no localizations further than those in the lymphedematous arm. This finding suggests that LE could have favoured the persistence of an occult localization of lymphoma, despite routine investigations evidenced an apparent complete remission of disease. Actually, the impaired lymphatic drainage could have rendered the involved area like a “pharmacologic sanctuary”, allowing lymphoma cells to skip the antiproliferative effect of chemotherapy. In addition, the eventual local immuno-deficiency, according to the hypothesis of the “immunocompromised district”, might have promoted the chemotherapy resistance of malignant cells.[8,9]
In conclusion, our experience emphasizes that, in assessing the response to chemotherapy of lymphoma patient with chronic LE, in addition to routine examinations, it should be performed a careful investigation of the involved extremity tailored to exclude residual tumour localizations.
References
- Paskett ED, Dean
JA, Oliveri JM, Harrop JP.
Cancer-related lymphedema risk factors, diagnosis, treatment, and
impact: a review. J Clin Oncol. 2012;30:3726-33. http://dx.doi.org/10.1200/JCO.2012.41.8574
PMid:23008299
- Sharma A, Schwartz
RA. Stewart-Treves
syndrome: Pathogenesis and management. J Am Acad Dermatol. 2012 Jun 7.
[Epub ahead of print] http://dx.doi.org/10.1016/j.jaad.2012.04.028
- Peyron N,
Dandurand M, Guillot B. Malignant tumors as complications of
lymphedema. J Mal Vasc 1993;18:293-8. PMid:8120459
- Moffatt CJ, Franks
PJ, Doherty DC et al. Lymphoedema: an underestimated health problem.
QJM 2003; 96:731–8. http://dx.doi.org/10.1093/qjmed/hcg126
PMid:14500859
- La Barbera EO,
Chiusolo P, Laurenti L, et
al. MiCMA: an alternative treatment for refractory or recurrent
Hodgkin's disease. Ann Oncol. 2000 Jul;11:867-71. http://dx.doi.org/10.1023/A:1008329127887
PMid:10997816
- d'Amore ES, Wick
MR, Geisinger KR, Frizzera
G. Primary malignant lymphoma arising in postmastectomy LE. Another
facet of the Stewart-Treves syndrome. Am J Surg Pathol. 1990;14:456-63.
http://dx.doi.org/10.1097/00000478-199005000-00005
PMid:2327551
- Vose JM. Mantle
cell lymphoma: 2012 update
on diagnosis, risk-stratification, and clinical management. Am J
Hematol. 2012;87:604-9. http://dx.doi.org/10.1002/ajh.23176
PMid:22615102
- Ruocco V, Schwartz
RA, Ruocco E.
Lymphedema: An immunologically vulnerable site for development of
neoplasms. J Am Acad Dermatol 2002; 47: 124-127. http://dx.doi.org/10.1067/mjd.2002.120909
PMid:12077591
- Ruocco V, Brunetti
G, Puca RV, Ruocco E.
The immunocompromised district: a unifying concept for lymphedematous,
herpes-infected and otherwise damaged sites. J Eur Acad Dermatol
Venereol 2009; 23: 1364-1373. http://dx.doi.org/10.1111/j.1468-3083.2009.03345.x
PMid:19548975